Cancer is a leading cause of death in men and women throughout the world. However, cancer represents a very heterogeneous group of neoplasms. Because of this heterogeneity, it is difficult to detect or diagnose the presence of cancer in a patient in early stages and the diagnosis of cancer has remained a very difficult task. It is known that cancer occurs because of some abnormality in a gene. A change or abnormality in a gene at its transcriptional level often can lead to the production of proteins which are relatively unique for the cancer cell. These proteins sometimes are useful as markers that are assayable from blood or tissue samples of a patient. A marker is any property which can be used to distinguish cancer from normal tissue and from other disease states. Most markers are antigenic proteins, for example, carcenoembryonic antigen (CEA), Alpha Fetoprotein (AFP), or prostatic specific antigen (PSA). Others include CA 125, CA 15-3, and CA 19-9. These antigens are usually detected by using the antibody which is relatively specific for these antigenic markers. The assays using these markers have not to date been markedly predictive of the presence of cancer in patients. The sensitivity and specificity of these antigenic marker assays has been relatively low. For any screening test to have sufficient utility in a clinical setting, it must display adequate sensitivity and specificity. Sensitivity is defined as the probability that a test will be positive given that the patient has the disease. Specificity of the test refers to the probability that the test will be negative provided that the disease is absent. In addition, many of the commercially available tests are only applicable to a narrow range of cancer types and these tests suffer not only from the disadvantage that other types of cancer may be missed, but also from the disadvantage that a narrow applicability of the tests requires running multiple tests on a single patient. The ideal marker is one that is specific and universal, resulting from the expression of the unique gene product in all kinds of transformed cancer cells.
Although, most cancer markers are antigenic proteins, some cancer markers are antibodies. For example, an anti-GAD2 antibody has been used in conjunction with the GAD2 antigenic protein to measure GAD2 antibody which occurs in hepatic cancer. The method of detecting the presence of autoantibodies on the fetalphosphal protein in patients having cancer is also known. U.S. Pat. No. 4,840,915 issued to Bogosh in 1989 describes the use of a tumor antigen called malignin to measure antibody as a cancer marker. In U.S. Pat. No. 5,866,690 Bogosh disclosed that malignin antibodies were IgM antibodies. In 2000, Thornthwaite published the results of a clinical study using the malignin antigen to measure antimalignin antibodies as cancer markers in breast cancer patients. Other cancer antigen markers were used for comparison in this clinical study which demonstrated that measurement of the malignin antibody was more sensitive (97%) in detecting breast cancer than the measurement of the antigens, CEA 0%, CA 15-3 (10%), CA 19-5 (5%), or CA 125 (16%).
Antibodies are immunoglobulins which combine antigens specifically. The use of antibodies and immunoassays for the detection of minute amounts of substances in physiological fluids is well known in the art. The assay basically depends on the binding interaction between an antigen and an antibody therefor. In the great majority of systems described in the prior art, the antibody is usually immunoglobulin G (IgG). Both polyclonal and monoclonal IgG's have been used. IgM is a well known 19S immunoglobulin which comprises about 7% of the immunoglobulins found in man. IgM antibodies are the earliest antibodies generated in the immune response. Although IgM antibodies tend to be very effective, especially in combating bacterial infections, they have a relatively short in vivo half life of about 5 days. The use of IgM antibodies has received relatively less attention in the immunoassay art in the diagnosis of cancer. IgM antibodies tend to aggregate and are relatively difficult to stabilize, especially in the purified form. They are very sensitive to reducing agents, they self-aggregate and precipitate out of solution, and have been found to bind in a nonspecific manner. Also, they are considered to have substantially less binding affinities for antigens than IgG antibodies. For these reasons, IgMs have not been utilized in immunoassays except in rare instances. One would not expect an IgM antibody to be useful to measure the presence of an antigen cancer marker.
The present invention provides new cancer markers utilizing an IgM antibody that is highly specific for a new cancer related antigen that appears to be common in a wide range of cancers. This cancer recognition system of the present invention provides a means for the detection of cancer in a broad range of cancers with relatively high selectivity and specificity. Furthermore, this novel antigen and its related antibody may also have utility in the treatment of cancers.